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1.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
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Actin cytoskeleton is crucial to support spermatogenesis in the mammalian testis. However, the molecular mechanism(s) underlying changes of actin cytoskeletal organization in response to cellular events that take place across the seminiferous epithelium (e.g., self-renewal of spermatogonial stem cells, germ cell differentiation, meosis, spermiogenesis, spermiation) at specific stages of the epithelial cycle of spermatogenesis remain largely unexplored. This, at least in part, is due to the lack of suitable study models to identify the crucial regulatory proteins and to investigate how these proteins work in concert to support actin dynamics. Much of the information on the role of actin binding proteins in the literature, namely the actin bundling proteins, actin nucleation proteins and motor proteins, are either findings based on genetic models or morphological analyses. While this information is helpful to delineate the function of these proteins to support spermatogenesis, they are not helpful to identify the regulatory signaling proteins, the signaling pathways and the cascade of events to modulate actin cytoskeleton dynamics. Recent studies based on the use of toxicant models, both in vitro and in vivo, however, have bridged this gap by identifying putative regulatory and signaling proteins of actin cytoskeleton. Herein, we summarize and critically evaluate these findings. We also provide a hypothetical model by which actin cytoskeletal dynamics in Sertoli cells are regulated, which in turn supports spermatid transport across the seminiferous epithelium, and at the blood-testis barrier (BTB) during the epithelial cycle of spermatogenesis. 相似文献
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Prabhakaran Dhanasekaran Swaminathan Rajavarman Sivasuriyanarayanan Vinod Selvaganesh Santoshkumar Dattatray Bhat 《Materials》2021,14(9)
Nanocrystalline platinum with different morphologies is synthesized via electrochemical deposition technique. The nucleation mechanism and its structural effect over the electrodeposited Pt on carbon electrodes have been systematically studied. Powder X-ray diffraction, X-ray photoelectron spectroscopy, and field-emission scanning electron microscopy are employed to study nucleation, oxidation states, and Pt structure growth on a carbon electrode. This study reports significant development of Pt metal nanoparticles with different morphologies such as a sphere, flower, core-flower, and rod-like structure directly fabricated on carbon electrode while tuning the deposition parameters such as current density, time, temperature, pH during the deposition process. The proposed electrochemical route represents a superior fabrication procedure for large-scale electrode fabrication compared to a conventional method for preparing membrane electrode assemblies for fuel cell stacks. 相似文献
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《The Journal of thoracic and cardiovascular surgery》2023,165(2):449-459.e4
ObjectiveThe objective of this study was to investigate the association between morphological variation and postsurgical pulmonary vein (PV) stenosis (PPVS) in patients with cardiac total anomalous pulmonary venous connection (TAPVC).MethodsThis single-center, retrospective study included 168 pediatric patients who underwent surgical repair of cardiac TAPVC from 2013 to 2019 (connection to the coronary sinus [CS], n = 136; connection directly to the right atrium [RA], n = 32). Three-dimensional computed tomography modeling and geometric analysis were performed to investigate the morphological features; their relevance to the PPVS was examined.ResultsThe connection type had no association with PPVS (CS type: 18% vs right atrial type: 19%; P = .89) but there was a higher incidence of PPVS in patients with a single PV orifice than > 1 orifice (P < .001). Confluence-to-total PV area ratio (hazard ratio, 4.78, 95% CI, 1.86-12.32; P = .001) and length of drainage route (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < .001) had a 4- and 1-fold increase in the risk for PPVS in the CS type after adjustment for age and preoperative pulmonary venous obstruction. In the right atrial type, those with anomalous PV return to the RA roof were more likely to develop PPVS than to the posterior wall of the RA (P < .001).ConclusionsThe number of inter-junction PV orifice correlated with PPVS development in cardiac TAPVC. The confluence-to-total PV ratio, length of drainage route, and anomalous PV return to the RA roof are important predictors for PPVS. Morphological subcategorization in this clinical setting can potentially assist in surgical decision-making. 相似文献
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Tarentola annularis is a climbing gecko with a wide distribution in Africa north of the equator. In the present paper, we describe the development of the osteocranium of this lizard, from the first appearance of the cranial elements up to the point of hatching. This is based on a combination of histology and cleared and stained specimens. This is the first comprehensive account of gekkotan pre-hatching skull development based on a comprehensive series of embryos, rather than a few selected stages. Given that Gekkota is now widely regarded as representing the sister group to other squamates, this account helps to fill a significant gap in the literature. Moreover, as many authors have considered features of the gekkotan skull and skeleton to be indicative of paedomorphosis, it is important to know whether this hypothesis is supported by delays in the onset of cranial ossification. In fact, we found the sequence of cranial bone ossification to be broadly comparable to that of other squamates studied to date, with no significant lags in development. 相似文献
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《The surgeon》2022,20(4):e100-e104
IntroductionUndescended testis (UDT) is a clinical diagnosis and a common reason for referral to paediatric urology outpatients. Our aim was to assess current referral patterns at our unit and to identify predictive factors that may better aid primary care physicians (PCP) in diagnosing UDT based on history and physical exam.MethodsA retrospective analysis of referrals to outpatients from 2014 to 2016 was performed to assess current referral patterns including referral source, age, reason for referral and outcome following assessment by a single consultant paediatric urologist.A prospective analysis of new referrals was performed to identify predictive factors which may aid in the diagnosis of UDT including gestational age, presence of scrotal asymmetry and previously obtained imaging.ResultsFrom 2014 to 2016, 259 boys were referred with suspected UDT. The majority of referrals were received from PCPs (62%) followed by Neonatology (29%), Paediatrics (8%) and general surgery (1%). Median age at time of assessment was 29 (5–180) months. One hundred and eight (41.7%) boys were diagnosed with UDT.There were 74 boys assessed prospectively. Median age at assessment was 24.5 (6–171) months. We identified 3 predictors of a diagnosis of UDT; history of prematurity (p = 0.001), UDT mentioned to the parents at birth (p = 0.027) and scrotal asymmetry on examination (p < 0.001). Greatest diagnostic inaccuracy was found in boys referred beyond one year of age (27.7%). In this cohort, the absence of all three risk factors was associated with a negative predictive value of 94.1%.ConclusionThe majority of boys with suspected UDT are referred beyond the age recommended for orchidopexy (6–12 months). The majority of boys referred for assessment did not have UDT. We have identified three predictive factors that may aid referring physicians when assessing boys, particularly those older than 1 year. 相似文献
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Joseph D. Westaby Susanna T. E. Cooper Khari A. Edwards Robert H. Anderson Mary N. Sheppard 《Clinical anatomy (New York, N.Y.)》2020,33(3):394-404
Congenital heart disease is a rare but important finding in adults who experience sudden death. Examination of the congenitally malformed heart has historically been considered esoteric and best left to those with expertise. The Cardiac Risk in the Young cardiovascular pathology laboratory based at St George's University of London has now received over 6,000 cases. Of these, 21 congenitally malformed hearts were retained for research and educational purposes. Hearts were assessed using sequential segmental analysis, and causes of death were adjudicated based on thorough macroscopic examination and histology. Congenital malformations that were encountered included atrial septal defects, ventricular septal defects, tetralogy of Fallot, and transposition of the great arteries in both its regular and congenitally corrected variants. Findings also included hearts with mirror-imaged and isomeric atrial appendages. Direct causes of death included myocardial fibrosis, pulmonary hypertension, and hemorrhage. A small but notable proportion did not reveal a substrate for arrhythmia, raising the question of whether the terminal event was due to the congenital heart disease itself, or an underlying channelopathy. Here, we demonstrate the value of simple sequential segmental analysis in describing and categorizing the cases, with the concept of the “morphological method” serving to identify the distinguishing features of the cardiac components. Clin. Anat. 33:394–404, 2020. © 2019 Wiley Periodicals, Inc. 相似文献